It is proposed to study transport of large molecules (molecular weights greater than 10,000) across capillary walls, through interstitial spaces and into lymphatics in mammalian tissues and organs. The specific goals are: 1) to determine the processes by which such large molecules penetrate the capillary walls, whether by diffusion or ultrafiltration through pores or by pinocytosis, 2) to identify physiological and pathological factors which can alter macromolecular transport across capillaries, 3) to investigate the way in which large molecules move through interstitial spaces into lymphatics and 4) to evaluate the function of macromolecular constituents of plasma and interstitial fluid in maintaining fluid balance across capillary walls. These goals will be approached experimentally by study of lymph flow rates and lymph : plasma concentration ratios of test macromolecular solutes (dextran fractions and proteins) under a variety of conditions. The studies proposed will add to our knowledge of how plasma and interstitial fluid volumes are normally maintained in health, and may increase our ability to correct disturbances of extracellular fluid balance in disease.